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Docosahexaenoic Acid (DHA) Decreases IL-6 and Prostaglandin-Endoperoxide Synthase 2 mRNA Expression and IL-6 Protein Release, While Increasing Resolvin D1 and CXCL8 mRNA Expression and Protein Release in BovineEndometrial Cells
Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Campus Isla Teja s/n, Universidad Austral de Chile, Valdivia 5090000, Chile
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Animals 2025, 15(17), 2545; https://doi.org/10.3390/ani15172545
Submission received: 18 July 2025
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Revised: 19 August 2025
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Accepted: 27 August 2025
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Published: 29 August 2025
(This article belongs to the Section Animal Physiology)
Simple Summary
Uterine inflammatory diseases, such as metritis or endometritis, in postpartum cows are a frequent health problem in dairy farms, with consequences on fertility, milk production, and treatment costs. Uterine immunity may be affected by changes that occur during the transition period in dairy cows; therefore, appropriate management strategies and a diet that enhances the immune response are crucial. Omega-3 rich diets have been proposed for their potential beneficial effects on cows, as they can improve reproductive parameters. Docosahexaenoic acid (DHA) is an omega-3 fatty acid mostly found in fatty fish and algae, with recognized anti-inflammatory effects in immune cells; however, its effects on bovine endometrial immunity are not clear. In this study, we used a bovine endometrial cell line and demonstrated that DHA reduced the production of some pro-inflammatory mediators and increased the amount of a chemoattractant for phagocytes. Also, DHA stimulated the production of resolvin D1, a pro-resolving mediator. In addition, DHA reduced the activation of signaling pathways involved in cellular activation. We also performed a metabolomics assay and detected changes in some metabolites that could affect inflammation. In conclusion, this study showed that DHA triggers anti-inflammatory and pro-resolving conditions in bovine endometrial cells but also increases the expression of a chemotactic factor, suggesting that DHA could have beneficial effects on postpartum endometrial immunity, preventing or improving uterine diseases in postpartum cows.
Abstract
The endometrial immune response in postpartum cows is key to maintaining uterine health and preventing inflammatory diseases such as metritis and endometritis. Appropriate management strategies and diets that enhance the immune response are crucial during the transition period; therefore, diets rich in omega-3 fatty acids have been proposed for their potential beneficial effects on cows. Docosahexaenoic acid (DHA) is an omega-3 fatty acid with anti-inflammatory effects in immune cells; however, its effects on bovine endometrial immunity are not fully known. This study aimed to determine the effect of DHA on the inflammatory response in bovine endometrial (BEND) cells. BEND cells were incubated with DHA without or with lipopolysaccharide (LPS), and the mRNA expressions of prostaglandin-endoperoxide synthase 2 (PTGS2), interleukin (IL)-6, and CXCL8 were analyzed using RT-qPCR. The protein amount of IL-6, or CXCL8, and Resolvin D1 (RvD1) in the cell culture medium were analyzed using ELISA. DHA significantly reduced the expression of LPS-induced IL-6 and PTGS2 but increased LPS-induced CXCL8 expression. In addition, DHA reduced LPS-induced ERK1/2 and Akt phosphorylation, as assessed by immunoblotting. DHA increased the production of RvD1, a metabolite of DHA, at 8 and 24 h. In addition, RvD1 reduced LPS-induced CXCL8 production and increased the phosphorylation of ERK1/2 and Akt. Finally, changes in metabolite levels, such as an increase in 2-hydroxypyridine in DHA-treated cells, were obtained using a metabolomic assay. In conclusion, DHA reduced IL-6 and PTGS2 mRNA expression and IL-6 protein release and increased RvD1 levels in bovine endometrial cells, which suggest that DHA could have beneficial effects on endometrial immunity. The increase in CXCL8 mRNA expression and protein release induced by DHA remains to be studied; however, it could play a role in the innate defensive mechanisms of phagocytes.
Keywords:
endometrial cell; docosahexaenoic acid (DHA); resolvin D1; inflammation; cows
